Drug therapies to nip allergies in the bud
From the June ACP Observer, copyright © 2003 by the American College of Physicians.
By Margie Patlak
Even as allergy season begins to fade in parts of the country, experts warn that you shouldn't be too quick to dismiss symptoms like watery eyes and nasal congestion as relatively harmless symptoms of allergic rhinitis.
A growing body of evidence shows that chronic allergies can lead to serious long-term effects. While many physicians may think the condition is relatively harmless, a 1999 report from the World Health Organization (WHO) suggested that allergic rhinitis can progress to asthma, which can become life-threatening.
With recent studies reaching the same conclusion, allergy experts are urging physicians to treat nasal allergies more aggressively. Instead of waiting for patients to complain about significant symptoms, they say, physicians should act on treating allergies before they become a problem.
The good news is that because drug makers have been steadily releasing new treatments for allergic rhinitis, you have more options than ever to treat the condition.
Early this year, the FDA approved the antileukotriene montelukast to treat allergic rhinitis, ushering a new class of allergy drugs into the treatment mix. At the same time, the number of antihistamines and nasal corticosteroids to treat allergies is growing.
But the boom in allergy drugs presents physicians with a problem: How to decide which is best for a particular patient. Here's an overview of some of the drug options to treat allergies.
The asthma link
In the executive summary of its December 1999 "Allergic Rhinitis and Its Impact on Asthma" workshop, the WHO stressed that allergic rhinitis is not a solitary disease. Instead, it is a complex syndrome that affects both the upper and lower airways. Both asthmatic and nonasthmatic patients with allergic rhinitis, the report pointed out, have some lower airway inflammation.
As a result, the WHO concluded that untreated allergic rhinitis could potentially trigger asthma attacks. It also suggested that allergic rhinitis may be a major risk factor for developing asthma.
One study found that nearly one-third of allergic rhinitis patients developed asthma within 10 years.
"Traditionally, physicians thought that you treat allergic rhinitis only if the patient is significantly bothered by it," said Mark S. Dykewicz, FACP, professor of internal medicine and director of the allergy and immunology training program at St. Louis University in St. Louis. "But in view of this link between allergic rhinitis and asthma, we should probably lower our threshold for treating rhinitis aggressively."
Recent clinical data have bolstered the link between allergies and more serious problems. In one survey of 99 patients reported in the January 2001 issue of Respiratory Medicine, nearly one-third of allergic rhinitis patients developed asthma within 10 years.
William W. Storms, FACP, an allergist and clinical professor of medicine at the University of Colorado Health Sciences Center in Colorado Springs, said that other recent studies have found that allergy shots given to nonasthmatic allergic rhinitis patients significantly lowered their incidence of developing asthma.
Still another study published in the April 2002 Journal of Allergy and Clinical Immunology found that asthmatic patients whose allergic rhinitis or other nasal conditions were treated with nasal corticosteroids had fewer emergency department visits for asthma than patients whose rhinitis goes untreated. (Experts caution that while the results may be encouraging, this study did not specifically examine controlling rhinitis.)
Even if you recognize the importance of treating allergic rhinitis, choosing medications can be overwhelming. There are five main drug types to treat some or all symptoms of allergic rhinitis: nasal cromolyn sodium, antihistamines, antileukotrienes, decongestants and nasal corticosteroids.
Each drug type addresses a different stage of the allergic reaction cascade. For example, nasal cromolyn administered prior to acute allergen exposure can reduce the early phase of that reaction. The drugs hamper mast cells' release of histamines and leukotrienes, key mediators that contribute to symptoms of allergic rhinitis. Once the body has released these chemicals, physicians can counteract their effects on tissue by blocking mediator receptors using antihistamines and antileukotriene agents.
Although all treatment guidelines include decongestants as an option, most don't highly recommend the drugs because of their side effects.
Several hours after the initial allergic reaction, late phase responses driven by inflammatory cells really start to kick in. These cells not only increase congestion, but they heighten other symptoms by directing mast cells to release more histamines and leukotrienes.
With continued allergen exposure, persistent late phase responses may occur. Nasal corticosteroids best hamper this inflammatory response, and researchers believe antileukotrienes also reduce some aspects of inflammation.
The associated inflammation also primes the lining of the nose to be more sensitive to the next batch of allergens it encounters, making nasal tissue "trigger happy," Dr. Dykewicz said.
Here are some of the pros and cons of various rhinitis treatments:
Nasal corticosteroids. Several comparison studies show that nasal corticosteroids taken once daily are the most effective medicines for allergic rhinitis. The drugs tackle all the allergic rhinitis symptoms: runny nose, sneezing, congestion, and itchy nose and throat. In addition, meta analysis has shown that nasal corticosteroids can relieve symptoms of allergic conjunctivitis as effectively as oral antihistamines.
Unlike antihistamines or antileukotrienes, many nasal corticosteroids don't act immediately. "If you have an allergic reaction after cutting the grass and you take a nasal steroid," Dr. Storms said, "you'll feel better two days later."
Experts point out that newer nasal corticosteroids like fluticasone (Flonase) act much more quickly. A study in the Nov. 26, 2001, Archives of Internal Medicine found that patients who took this drug as needed to treat allergic rhinitis fared better than those taking the antihistamine loratadine (Claritin) as needed.
Another major drawback to nasal corticosteroids? Patients have to administer the drugs with nose sprays. Some patients can't stand inserting anything in their nose, while others complain of the drugs' taste, smell or resulting nasal irritation. For many patients, pills are literally easier to swallow.
According to a study published in the September 2002 Annals of Allergy, Asthma and Immunology, however, patients may tolerate some sprays better than others. Researchers found that patients rated triamcinolone (Nasacort) as significantly superior to fluticasone and mometasone (Nasonex) in terms of comfort during administration, nasal irritation, odor, taste and aftertaste.
Antihistamines. Although not as effective as nasal corticosteroids, oral antihistamines act quickly to relieve hallmark symptoms like itching, sneezing and runny nose. Nasal congestion is less effectively treated with this drug class, although newer nonsedating antihistamines like fexofenadine (Allegra) and desloratadine (Clarinex) have been shown to ease congestion. So has the low-sedating antihistamine cetirizine (Zyrtec).
(One study, however, found that loratadine—one of the most popular nonsedating antihistamines—does not relieve congestion as effectively as fexofenadine.)
With many long-acting antihistamines, patients have to take only one pill a day during their allergy season or as needed for more occasional allergies. Nasal antihistamines like azelastine (Astelin) are at least as effective as oral antihistamines. (Some data, however, have suggested that azelastine may offer an intermediate level of effectiveness between oral antihistamines and nasal corticosteroids.) Because these drugs can have a bitter taste and cause some sedation, however, patients often prefer oral antihistamines.
Antileukotrienes. Antihistamines now face competition from a new class of allergy medicines that inhibit the leukotrienes released during an allergic reaction. Three antileukotrienes are available in the United States, but most are approved to treat only asthma. Only montelukast (Singulair) is approved for treating allergic rhinitis.
Researchers have extensively tested the drug and found it relieves all the symptoms of allergic rhinitis, including congestion, with no more side effects than a placebo.
As Dr. Storms pointed out, however, "We don't know how effective montelukast is compared to other options." A recent study in the Journal of Allergy and Clinical Immunology found that nasal fluticasone was more effective than the combination of montelukast and loratadine. More studies are needed.
Cromolyn. Nasal cromolyn sodium is a less popular allergic rhinitis treatment, in large part because the drug has several drawbacks.
For one, patients must take it nasally at least four times a day. Cromolyn is also not as effective as other allergy medicines and has to be taken before allergen exposure to be effective. But because it's a fairly safe drug, physicians often prescribe it to pregnant women suffering from allergic rhinitis.
Decongestants. Although decongestants are the best medication to relieve a stuffy nose, serious side effects often limit their use.
Oral decongestants can trigger tachycardia, hypertension, insomnia and anxiety. Oral decongestants also can aggravate prostate problems and glaucoma. And because they have been associated with birth defects (gastroschisis, an abnormal development of the abdominal wall), they are best avoided in pregnant women during the first trimester.
Topical decongestants, available over the counter in nasal sprays such as oxymetazoline (Afrin) and phenylephrine (Neo-Synephrine), lack these potentially dangerous side effects. When taken for more than five days, however, they can cause rebound congestion, with initial relief followed by worsening congestion. Some patients can develop dependence on these sprays to avoid this rebound effect.
Experimental options. Omalizumab (Xolair) is a potential newcomer to the allergy treatment scene. The drug contains a monoclonal antibody that targets immunoglobulin E (IgE), the kingpin in allergic reactions that causes mast cells to become sensitized to allergens.
The FDA is currently considering whether the drug should be approved for use in patients with allergy-related asthma. Some studies have also found that omalizumab is effective for treating allergic rhinitis, although comparison studies with other agents have not been published. "Unlike conventional allergen immunotherapy injections that can significantly benefit the long-term course of allergic rhinitis, anti-IgE would not be expected to offer this benefit," Dr. Dykewicz said.
With experts predicting that Xolair may cost more than $1,000 a month to treat asthma, "I don't believe pharmacy benefit plans would allow doctors to prescribe it for allergic rhinitis," Dr. Dykewicz said.
The right medicine
With so many treatment options available, you need to consider several factors when choosing medications. Here is a review of appropriate treatments based on the severity of patient symptoms:
Mild, intermittent symptoms. For patients with mild and intermittent symptoms, most experts agree that nonsedating oral antihistamines are your best bet.
Steer clear of older antihistamines, such as chlorpheniramine, that can cause drowsiness. Studies show these drugs can impair patients' driving ability and job performance without them even being aware that they are getting sleepy or slowing down mentally.
Older antihistamines do offer one big advantage: They are much less expensive than the newer, nonsedating drugs. If cost is a major consideration, patients may prefer older antihistamines. (Experts predict this trend may become more pronounced now that Claritin is available over the counter.)
"Many pharmacy benefit plans are now either dropping coverage or increasing co-pays for second-generation antihistamines," said Dr. Dykewicz. "Ironically, the over-the-counter status for loratadine and the ensuing higher cost to patients for second-generation antihistamines may promote greater use of the cheaper, sedating, first-generation antihistamines we've discouraged them from using." (For more, see "Patients who self-treat their allergies: a growing problem?")
Montelukast is another option for patients with mild, intermittent allergies. Treatment guidelines, however, have not yet defined how to fit montelukast into the treatment picture, and experts disagree about when it should be used.
For patients with persistent allergic rhinitis, Dr. Storms said he would try either montelukast or a nonsedating antihistamine and then add a nasal steroid if necessary. Because Claritin is now sold over the counter, most patients have already tried this option, he explained, so using montelukast may make sense in those patients.
But Dr. Dykewicz doesn't feel the evidence is strong enough yet to recommend an antileukotriene as a single, first-line treatment for allergic rhinitis. He would, however, consider giving it to patients who don't respond to an antihistamine or nasal corticosteroid.
Persistent, mild symptoms. For patients with persistent, mild symptoms, first-line treatment options should include a nasal corticosteroid. You can combine an antihistamine with an antileukotriene, but research has produced conflicting data about this strategy's effectiveness. One thing is clear: Taking two drugs is more expensive than using a nasal corticosteroid alone.
Which option should you recommend for patients with mild, persistent rhinitis? Experts say the answer depends primarily on symptoms. "If patients have a lot of sneezing or itching," Dr. Storms said, "we give them an antihistamine or montelukast. If they have more congestion, mucus and post-nasal drip, then we try to convince them to take a nasal steroid every day."
Dr. Dykewicz said that patient preference is another important factor. "Some people won't stick anything up their noses," he explained, "while others say 'I don't want drugs going throughout my entire body. I just want medicine going where I need it-to the nose,'" he said. "For patients with mild symptoms, I'll explain the options and let them choose."
Moderate to severe symptoms. For persistent, moderate to severe symptoms that disrupt sleep and daily activities, experts recommend a nasal corticosteroid with or without an oral antihistamine, or antileukotriene. Dr. Storms said most patients in this category need more than one drug to control their symptoms.
Because of their side effects, decongestants can be problematic, even for patients whose main complaint is congestion. "I recommend decongestants for younger rhinitis patients with congestion who don't respond to antihistamines, montelukast or nasal steroids, or for patients who have more sinus problems associated with their allergies," Dr. Storms said. Although all treatment guidelines include decongestants, he added, "They don't highly recommend the drugs."
Whatever you recommend to patients, even if it's an over-the-counter medication, be sure to follow up within a few weeks with a phone call or scheduled office visit to make sure the patient's symptoms are under control, said Dr. Storms.
"A number of my patients claim their primary care physician told them to try something over the counter, but it didn't work," he said. "They assumed that was all the doctor had to offer."
Margie Patlak is a freelance science writer in Elkins Park, Pa.
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
With so many allergy medicines now available over the counter, more patients will likely be treating allergies without consulting a doctor. That can be a problem, particularly because studies show that self-treatment is often not successful.
One survey of patients with allergic rhinitis, many of whom were self-treating, found that 75% of them felt their allergies were not well-controlled. Another survey found that 91% of allergy sufferers use over-the-counter allergy medications—yet less than 10% said they chose a medication based on a doctor's recommendation. In addition, these patients said they tried an average of five different over-the-counter allergy medications before finding one that works, while almost all of these patients experienced side effects from the drugs.
Self-medicating can also be downright dangerous. University of Colorado allergist William W. Storms, FACP, recalled one patient with heart disease who developed an arrhythmia after taking over-the-counter Claritin-D, which is an antihistamine combined with a decongestant.
Because so much self-treatment occurs, "internists should go out of their way to find out whether their patients have allergic rhinitis," Dr. Storms said. "This is a very common disease that harms quality of life, yet it's very easy to treat with drugs that have no side effects. If internists show concern about these kinds of less serious conditions, their patients will walk out of their offices a lot happier."
Studies suggest that as many as 25% of patients diagnosed with allergic rhinitis don't actually have the condition. When allergic rhinitis is persistent instead of seasonal, it shares many symptoms with other ailments. So how can you be sure that a patient with a runny nose, congestion and sneezing has an allergy?
Unfortunately, there's no easy answer. The common wisdom to distinguish an allergy from a cold or sinus infection is that an allergy tends to cause more itching in the nose, throat and eyes, as well as "allergic shiners"—a darkening of the skin under the eyes.
Allergy patients often have swollen, pale or bluish nasal membranes. And allergies tend to give patients clear nasal discharge, whereas a cold or sinusitis causes thick, yellow or green discharge.
But no studies have ever tested the accuracy of these assumptions. "These are good, supportive clues," said University of Colorado allergist William W. Storms, FACP. "But if you don't see these symptoms, you shouldn't rule out allergic rhinitis. For many allergic rhinitis patients, a physical exam won't reveal anything abnormal."
Seasonal allergic rhinitis is easier to diagnose because symptoms appear when patients are exposed to large amounts of allergens. "Patient symptoms will correlate closely to high pollen counts," said Dr. Storms.
(The National Allergy Bureau tracks and reports regional outdoor pollen levels for the entire country.)
One of the best ways to diagnose allergies is to try allergy treatments and see if they relieve patients' symptoms, he said.
But if you still aren't sure, order serum tests for the immunoglobulin E (IgE) specific to the allergens that are the likely culprits based on the patient's history. "If the patient has a dog, for example, test her for dog dander allergies," said Dr. Storms.
Serum IgE tests are about 80% accurate. But if serum IgE tests don't confirm your hunch about a patient's allergy, try skin testing, which is more invasive but also more reliable. Thanks to recent improvements in the allergy extracts used for skin testing, these prick tests are now more than 99% accurate for identifying allergies to pollens, dust mites, animals, molds and foods.
If you decide to test your patients for allergies yourself rather than referring them to an allergist, be prepared to deal with the results, said Mark S. Dykewicz, FACP, professor of internal medicine and director of the allergy and immunology training program at St. Louis University in St. Louis.
"Patients will need a fair amount of education and follow up visits," he said. "That can take more time than many internists are willing to spend."
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